Drug delivery device with a rotatable drive mechanism

ABSTRACT

A rotatable drive mechanism for a drug delivery device may include a lead screw having a distal end, a proximal end, and external threads, a bearing, and a ball screw driver having a threaded aperture wherein the threaded aperture is configured to rotatably engage with the external threads of the lead screw. The mechanism may further include a biasing device disposed between the bearing and the ball screw driver generating an axial drive force, and an activation device configured to release the biasing device and allowing the biasing device to expand from a compressed position to an extended position through which the axial drive force of the biasing device causes the ball screw driver to axially move toward the distal end of the lead screw and rotate the lead screw such that a threaded engagement between the lead screw and the ball screw driver bears the axial drive force.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/651,720, filed Jul. 17, 2017, which claims the priority benefit ofU.S. Provisional Appl. No. 62/365,185, filed Jul. 21, 2016, the entirecontents of which are incorporated herein by reference.

FIELD OF TECHNOLOGY

The present disclosure is directed to a drug delivery device and, moreparticularly, to a drug delivery device with a rotatable drive mechanismhaving a lead screw.

BACKGROUND

Drug delivery devices, such as autoinjectors and hand-held injectors,are commonly prescribed for patients to self-administer medication. Suchdevices typically include a drive mechanism (e.g., a spring) thatoperates on a prefilled syringe in response to a triggering event, suchas the patient pressing a button on the device. The drive mechanismcreates a drive force and, additionally, operates on a plunger todeliver the medication subcutaneously via the needle. These drugdelivery devices may be constructed as single-use or reusable devices.Autoinjectors offer several benefits in drug delivery over conventionalsyringes, such as simplicity of use. Autoinjectors are beneficial fordelivering drugs with high viscosities. However, as viscosity increases,the drive force required to inject the drug also increases. A largedrive force may cause internal pressure build-up within the device,causing the prefilled syringe to fracture during injection.

FIG. 1 illustrates a known autoinjector 10 that includes a reservoir 12configured to contain and/or containing a drug 11, a drug deliverymember 14 configured to deliver the drug, a plunger rod 16 configured todrive a plunger 18, and a drive mechanism 20 configured to power drugdelivery. The reservoir 12 in this example is a glass syringe andincludes a thin-walled glass barrel 13.

The drive mechanism 20 includes a compressed coil spring 21 coupled tothe plunger rod 16 and is configured to deliver an initial force to movethe plunger rod 16 from a preloaded position where the plunger rod 16 isspaced away from the plunger 18, to a second position where the plungerrod 16 makes contact with the plunger 18. Upon actuation of the drivemechanism 20, this conventional autoinjector 10 can experience an impactevent (not shown), where the drive force initially causes the plungerrod 16 to impart an impact force on the plunger 18 before causing theplunger 18 to move through the reservoir 12. As the plunger 18 movesthrough the reservoir 12, a stopper 15 of the plunger 18 is configuredto sealingly and slidably engage an inner wall of the glass barrel 13 topush the drug 11 through the reservoir 12 and out through an open end ofthe drug delivery member 14.

Based on the requirements of the drug 11 and the force generated by thedrive mechanism 20 (i.e., a high viscosity drug may require a higherdrive force to move the plunger 18 through the reservoir 12), theplunger rod 16 may indirectly or directly impart impact forces onto thebarrel 13 of the reservoir 12 when the plunger rod 16 impacts theplunger 18. Large forces could break the barrel 13. If the plunger 18 isplaced lower in the reservoir 12, the impact becomes more likely tocause breakage. A load from the impact event generates pressure waves inthe drug 11 that propagate through the glass barrel 13. For thecombination of materials and geometries typical of glass syringes, apressure wave will “couple” to the glass barrel 13 of the reservoir 12as it propagates axially. The coupled wave oscillates through the barrel13 and may cause the barrel 13 to fracture.

SUMMARY

The present disclosure minimizes the risk of component failure due toimpact forces of a spring-loaded drug delivery device. Specifically, thepresent disclosure includes a drug delivery device with a rotatabledrive mechanism that bears the load of the drive force rather thanimparting an impact force on a glass-walled reservoir of the drugdelivery device. In accordance with one or more aspects describedherein, a rotatable drive mechanism of a drug delivery device mayprovide a safe drive system capable of variable injection rates,deliverable volumes, and drug viscosities without compromising integrityof components of the drug delivery device.

In accordance with a first exemplary aspect, a rotatable drive mechanismfor a drug delivery device may include a lead screw having a distal end,a proximal end, and external threads, a bearing operably attached to theproximal end of the lead screw, a ball screw driver having a threadedaperture, wherein the threaded aperture is configured to rotatablyengage with the external threads of the lead screw, the ball screwdriver and lead screw being coaxially aligned. The drive mechanism mayfurther include a biasing device disposed between the bearing and theball screw driver generating an axial drive force for biasing the ballscrew driver away from the bearing. Further, the drive mechanism mayinclude an activation device configured to release the biasing deviceand allowing the biasing device to expand from a compressed position toan extended position through which the axial drive force of the biasingdevice causes the ball screw driver to axially move toward the distalend of the lead screw and rotate the lead screw such that a threadedengagement between the lead screw and the ball screw driver bears theaxial drive force.

In accordance with a second exemplary aspect, a drug delivery device mayinclude a reservoir having a distal end and proximal end, a drugdelivery member in fluid communication with the distal end of thereservoir, a plunger disposed in and moveable relative to the reservoir,a drive mechanism including a lead screw having a distal end, a proximalend, and external threads, a bearing operably attached to the proximalend of the lead screw, a ball screw driver having a threaded aperture,wherein the threaded aperture is configured to rotatably engage with theexternal threads of the lead screw, the ball screw driver and lead screwbeing coaxially aligned, a biasing device disposed between the bearingand the ball screw driver generating an axial drive force for biasingthe ball screw driver away from the bearing. The drive mechanism mayfurther include an activation device configured to release the biasingdevice and allowing the biasing device to expand from a compressedposition to an extended position through which the axial drive force ofthe biasing device causes the ball screw driver to axially move towardthe distal end of the lead screw and rotate the lead screw such that athreaded engagement between the lead screw and ball screw driver bearsthe axial drive force.

In accordance with a third exemplary aspect, a rotatable drive mechanismfor a drug delivery device may include a lead screw having a distal end,a proximal end, and external threads, a bearing operably attached to theproximal end of the lead screw, a ball screw driver having a threadedaperture, wherein the threaded aperture is configured to rotatablyengage with the external threads of the lead screw, the ball screwdriver and lead screw being coaxially aligned, a biasing device disposedbetween the bearing and the ball screw driver generating an axial driveforce for biasing the ball screw driver away from the bearing, and anactivation device configured to release the biasing device and allowingthe biasing device to expand from a compressed position to an extendedposition through which the axial drive force of the biasing devicecauses the ball screw driver to axially move toward the distal end ofthe lead screw and rotate the lead screw such that a threaded engagementbetween the lead screw and ball screw driver bears the axial driveforce. The rotatable drive mechanism may further include a planetarygear coupler having a sun gear, a plurality of satellites, and aplurality of satellite shafts, wherein the sun gear receives a firstrotational velocity from the lead screw and delivers a second rotationalvelocity to the satellite shafts via the satellites. Further, atelescoping plunger assembly may include an actuator, a plunger rod, anda plunger, the actuator being coupled to the satellite shafts at aninput and coupled to the plunger rod at an output, the actuator beingconfigured to receive a rotational velocity from the satellite shaftsand deliver a drive force to the plunger rod wherein the plunger rodaxially moves the plunger in a distal direction.

In accordance with a fourth aspect, a drug delivery device may include areservoir containing a drug, a drug delivery member in fluidcommunication with the reservoir, a plunger disposed in and moveablerelative to the reservoir, and a drive mechanism. The drive mechanismmay include a lead screw having external threads, and a planetary gearcoupler operatively coupled to the external threads of the lead screw.The planetary gear coupler may be configured to drive the lead screw ina axial direction. A biasing device may generate a rotational velocitydeliverable to the planetary gear coupler. An activation device may beconfigured to release the biasing device and allow the biasing device toexpand from a compressed position to an extended position through whichthe rotational velocity of the biasing device causes the lead screw torotate.

In further accordance with any one or more of the foregoing first,second, third, and fourth aspects, the rotatable drive mechanism for adrug delivery device and a drug delivery device may include any one ormore of the following forms.

In one form, the rotatable drive mechanism may include a planetary gearcoupler having a carrier arm, a sun gear, a plurality of satellites, anda plurality of connector shafts, wherein the carrier arm may receive afirst rotational velocity from the lead screw and delivers a secondrotational velocity to the satellites via the connector shafts, whereinthe satellites may deliver a third rotational velocity to the sun gear.

In one form, the rotatable drive mechanism may include a plunger rodthreadably coupled to the sun gear, wherein the sun gear delivers afourth rotational velocity to the plunger rod to axially move theplunger rod in a distal direction.

In one form of the drive mechanism, the first rotational velocity may begreater than the second rotational velocity.

In one form of the drive mechanism, the second rotational velocity maybe less than the first rotational velocity.

In one form, the drive mechanism may include a clutch mounted to thelead screw to reduce a rotational velocity of the lead screw.

In one form, the clutch may be an electromechanical clutch.

In one form, the drug delivery device may include a plunger rod having adistal end and a proximal end, the distal end of the plunger rod beingadjacent to the plunger and the proximal end being adjacent to the ballscrew driver, and wherein the ball screw driver is configured to axiallymove the plunger rod as the ball screw driver axially moves toward thedistal end of the lead screw.

In one form, the clutch may further include a dial mechanically coupledto the clutch, wherein the clutch may reduce the rotational velocity ofthe lead screw at a first rate by rotating the dial to a first positionand a second rate when the dial is in a second position.

In one form, the drug delivery device may include a housing containingthe planetary gear coupler. The planetary gear coupler may include aplanetary ring fixed to the housing, a carrier arm, a sun gear, aplurality of satellites, and a plurality of connector shafts.

In one form of the drug delivery device, the carrier arm may receive afirst rotational velocity from the biasing device and delivers a secondrotational velocity to the satellites via the connector shafts, andwherein the satellites deliver a third rotational velocity to the sungear.

In one form of the drug delivery device, the biasing device may be atorsion spring operatively coupled to the planetary gear coupler suchthat when the activation device releases the torsion spring, the torsionspring causes the planetary gear coupler to rotate the lead screw anddrive the lead screw in the axial direction.

In one form of the drug delivery device, the torsion spring may be fixedto the planetary ring and operatively coupled the carrier arm, such thatthe torsion spring applies a torque to the carrier arm when the torsionspring is released by the activation device.

In one form of the drug delivery device, the lead screw may bethreadably coupled to the sun gear, and the sun gear delivers a fourthrotational velocity to the lead screw to axially move the lead screw inthe distal direction.

In one form of the drug delivery device, the planetary ring may includea top portion, a bottom portion, and a deformable member disposedbetween the top and bottom portions, the top portion rotatable relativeto the housing and the bottom portion fixed to the housing. Thedeformable member may be configured to deform and absorb a torsionalshock when the torsion spring is released.

In one form of the drug delivery device, the biasing device may be acompression spring.

In one form, the drug delivery device may include a bearing operablyattached to a proximal end of the lead screw, and a ball screw driverhaving a threaded aperture. The threaded aperture may be configured torotatably engage with the external threads of the lead screw, and theball screw driver and lead screw may be coaxially aligned. The biasingdevice may be a compression spring disposed between a bearing and theball screw driver generating an axial drive force for biasing the ballscrew driver away from the bearing.

BRIEF DESCRIPTION OF THE DRAWINGS

It is believed that the disclosure will be more fully understood fromthe following description taken in conjunction with the accompanyingdrawings. Some of the drawings may have been simplified by the omissionof selected elements for the purpose of more clearly showing otherelements. Such omissions of elements in some drawings are notnecessarily indicative of the presence or absence of particular elementsin any of the example embodiments, except as may be explicitlydelineated in the corresponding written description. Also, none of thedrawings is necessarily to scale.

FIG. 1 illustrates a conventional spring-loaded autoinjector susceptibleto syringe fracture.

FIG. 2 illustrates a first exemplary drug delivery device having arotatable drive mechanism with a lead screw and planetary gear couplerpower pack in a preloaded configuration.

FIG. 3 illustrates a variation of the first exemplary drug deliverydevice.

FIG. 4 illustrates the rotatable drive mechanism of the first exemplarydrug delivery device of FIG. 3 in the preloaded configuration.

FIG. 5 illustrates the rotatable drive mechanism of the first exemplarydrug delivery device of FIGS. 3 and 4 in an extended position.

FIG. 6 illustrates a second exemplary drug delivery device having arotatable drive mechanism with a lead screw in a preloadedconfiguration.

FIG. 7 illustrates the rotatable drive mechanism of the second exemplarydrug delivery device of FIG. 6 in the preloaded configuration.

FIG. 8 illustrates the rotatable drive mechanism of the second exemplarydrug delivery device of FIGS. 6 and 7 in an extended position.

FIG. 9 illustrates a third exemplary drug delivery device having arotatable drive mechanism with a lead screw and a second exemplaryplanetary gear coupler power pack in a preloaded configuration.

FIG. 10 illustrates a cross-sectional view of the planetary gear couplerpower pack of FIG. 9, taken generally along plane X-X.

FIG. 11 illustrates a fourth exemplary drug delivery device having arotatable drive mechanism with a third exemplary planetary gear couplerpower pack in a preloaded configuration.

FIG. 12 illustrates a cross-sectional view of the planetary gear couplerpower pack of FIG. 11, taken generally along plane Y-Y.

FIG. 13 illustrates a partial view of a variation of the third exemplaryplanetary gear coupler power pack of FIG. 11 having a shock absorber.

FIG. 14 illustrates a schematic of the shock absorber in the variationof the third exemplary planetary gear coupler power pack of FIG. 13.

DETAILED DESCRIPTION

The rotatable drive mechanisms and drug delivery devices described andillustrated herein allow for variable volume delivery without loading aprefilled syringe. Each of the drug delivery devices includes arotatable drive mechanism powered by a biasing device, which drives therotatable drive mechanism to move a lead screw and/or plunger rod fordrug delivery. A first exemplary embodiment of a drug delivery device inFIGS. 2-5 has a lead screw and planetary gear coupler power pack, whichmay be used to control the speed of the plunger rod through the drugdelivery device according to the requirements of the drug. In FIGS. 6-8,a second exemplary embodiment of a drug delivery device has a simplifiedrotatable drive mechanism having a lead screw and plunger assembly.FIGS. 9 and 10 illustrate a third exemplary embodiment of a drugdelivery device having a rotatable drive mechanism including a leadscrew and a different planetary gear coupler power pack. Finally, FIGS.11-14 illustrate another embodiment of a drug delivery device with athird exemplary planetary gear coupler power pack used to power drugdelivery.

Turning first to FIG. 2, the first exemplary drug delivery device 100includes a rotatable drive mechanism 120 which powers drug delivery.Similar to the drug delivery device 10 of FIG. 1, the drug deliverydevice 100 includes a drug reservoir 112, which may be a prefilledsyringe, and includes a glass cylindrical barrel 113 configured tocontain the dispensable fluid 111 until delivery. A drug delivery member114 is in fluid communication with the reservoir 112 and delivers thedispensable fluid 111 subcutaneously to a patient. A plunger 154 isdisposed and movable within the reservoir 112 and is configured tosealingly and slidably engage an inner wall of the barrel 113 to pushthe drug 111 through the reservoir 112 and out through an open end ofthe drug delivery member 114. FIG. 3 illustrates a variation on the drugdelivery device 100 depicted in FIG. 2 and is identical to the drugdelivery device 100 in FIG. 2, but for the fact that it includes anadditional stopper 118 that is driven by the plunger 154 through thereservoir 112 by the rotatable drive mechanism 120. The stopper 118 is aseparate component from the plunger 154 and is engaged by the plunger154 during drug delivery.

The rotatable drive mechanism 120 of the drug delivery device 100 shownin FIGS. 2 and 3 is detailed further in FIGS. 4 and 5, and can also bereferred to herein as a drive assembly. As shown in FIGS. 2-5, therotatable drive mechanism 120 includes a lead screw 122, a bearing 124,a ball screw driver 126, a biasing device 128, and an activation device130. The lead screw 122 is a threaded shaft with a proximal end 132 anda distal end 134, and includes external threads 136 extending betweenthe proximal end 132 and the distal end 134. In other embodiments, thelead screw 122 may be partially threaded. The number of external threads136 may vary depending on the drive force desired or required forinjection and is discussed in more detail below. The ball screw driver126 includes an aperture 138 having internal threads 140 that engage theexternal threads 136 of the lead screw 122. The ball screw driver 126and the lead screw 122 are coaxially aligned along a longitudinal axis Aof the drug delivery device 100 when the ball screw driver 126 and thelead screw 122 are threadably engaged.

As illustrated in FIGS. 2-4, the bearing 124 is spaced apart from theball screw driver 126 by the biasing device 128. The biasing device 128,which is a compressed coil spring, generates an axial drive force F_(D)for biasing the ball screw driver 126 away from the bearing 124 whenreleased by the activation device 130. The activation device 130 isconfigured to release the biasing device 128 from the compressedposition as shown in FIG. 4, also referred herein as a preloadedconfiguration, to an extended position as shown in FIG. 5. As thebiasing device 128 expands from the compressed position to the extendedposition, the axial drive force F_(D) of the biasing device 128 causesthe ball screw driver 126 to axially move toward the distal end 134 ofthe lead screw 122. Simultaneously, a threaded engagement between theexternal and internal threads 136 and 140 of the lead screw 122 and theball screw driver 126 causes the lead screw 122 to rotate and bear theaxial drive force H. The bearing 124 is operably attached, either by aball bearing or other suitable mechanism, to the proximal end 132 of thelead screw 122, allowing the lead screw 122 to freely rotate withoutmoving axially after the biasing device 128 is released. The rotatabledrive mechanism 120 of the device in FIGS. 2-5 and, more specifically,the external threads 136 of the lead screw 122, bears the axial driveforce F_(D) instead of the glass barrel 113 of the reservoir 112.

The activation device 130, shown in the preloaded configuration in FIG.4, includes a button 133, an actuating spring 135, and a plurality oftabs 137. The actuating spring 135 is extended and disposed between thebutton 133 and the bearing 124. To release the biasing device 128, thebutton 133 is pressed downward, biasing the actuating spring 135 andcausing the button 133 to outwardly displace the tabs 137 away from theball screw driver 126 and lead screw 122. The biasing device 128 isreleased by the tabs 127 and expands into the extended position as shownin FIG. 5. The activation device 130 illustrated herein is merely anexample, and may be any activation device that can retain the compressedbiasing device 128 until it is triggered to release the compressed coilspring 128 for injection.

To vary the rate of injection, the spring rate of the biasing device 128may be changed, and as mentioned earlier, the external threads 136 ofthe lead screw 122 and the internal threads 140 of the ball screw driver126 may also vary. The rotational speed of the lead screw 122 may changeby increasing the spacing between threads 136 and/or decreasing orincreasing the number of threads 136. In some embodiments, the drugdelivery device 100 can also include a power pack that may be changed tovary the injection rate.

For example, the drug delivery device 100 of FIGS. 2-5 includes aplanetary gear coupler power pack 141, also referred herein as theplanetary gear coupler, that can be used to change the injection rate.The distal end 134 of the lead screw 122 is coupled to the planetarygear coupler power pack 141, which receives an input rotational velocityfrom the lead screw 122 and delivers a second output velocity. In theillustrated example, the planetary gear coupler power pack 141, alsoreferred herein as a planetary gear coupler, is operably coupled to atelescoping plunger assembly 142 that receives the second outputrotational velocity of the power pack 141 and drives the plunger 154through the reservoir 112. FIG. 4 illustrates an enlarged view of theplanetary gear coupler 141 and telescoping assembly 142 when theplanetary gear coupler 141 and the telescoping assembly 142 are in acompact configuration. The term “input rotational velocity” is used todescribe the rotational velocity of the lead screw 122, and may also bereferred to as “input velocity” or “first rotational velocity.” The term“output rotational velocity” is used to describe the rotational velocitythat the planetary gear coupler 141 delivers after receiving the inputrotational velocity, and may also be referred to as a “second velocity”or a “second rotational velocity.”

The planetary gear coupler power pack 141 of the drug delivery device100 described herein is epicyclical and includes a central sun gear 144and a plurality of orbiting gears 146 that rotate about the sun gear144. The orbiting gears 146, also referred herein as satellite gears,are smaller in size than the sun gear 144 by a certain degree or gearratio based on the requirements of the drug delivery device 100. Thegear ratio of the satellite gears 146 and the sun gear 144 may vary toeither increase or decrease output rotational velocity. The planetarygear coupler 141 of FIGS. 2-5 is a single stage planetary gear coupler141 in which the input rotational velocity of the lead screw 122 isconverted in one stage to either a higher or lower output rotationalvelocity. Other embodiments may include a multiple-stage planetary gearcoupler that may either reduce or magnify the input rotational velocityof the lead screw 122 to varying degrees, which may be controlled by auser by activating or deactivating one or more stages. The planetarygear coupler 141 includes a plurality of satellite shafts 148, eachsatellite shaft 148 being coaxially aligned with a longitudinal axis ofone of the satellite gears 146 and configured to deliver the outputrotational velocity. For example, in operation the sun gear 144 receivesa first rotational velocity from the lead screw 122 and delivers asecond rotational velocity to the satellite shafts 148 via thesatellites 146. The satellite shafts 148 deliver the second rotationalvelocity to the telescoping plunger assembly 142.

FIG. 5 illustrates the biasing device 128 and the telescoping plungerassembly 142 in the extended position. The telescoping plunger assembly142 in FIGS. 4 and 5 is activated by an actuator 150 and includes aplunger rod 152, the plunger 154, a first telescoping connector 160, anda second telescoping connector 162. The actuator 150 has an input port156 and an output port 158 where the input port 156 is coupled to theplanetary gear coupler 141 via the satellite shafts 148, for example,and the output port 158 is coupled to the plunger rod 152. In operation,the actuator 150 receives an input rotational velocity, e.g. the secondrotational velocity, from the satellite shafts 148 and actuates thetelescoping plunger assembly 142 in a distal direction. An open sleeve164 may be attached to the plunger assembly 142 to protect thetelescoping plunger assembly from external forces and contamination.

The telescoping plunger assembly 142 may gradually extend from thecompressed position shown in FIG. 4, to an extended position shown inFIG. 5 by rotating the plunger rod 152. When the plunger rod 152rotates, each of the first telescoping connector 160 and the secondtelescoping connector 162 rotates until each connector occupies theextended position as depicted in FIG. 5. In the example illustratedherein, the actuator 150 rotates the plunger rod 152 relative to thefirst telescoping connector 160, thereby axially displacing the firsttelescoping connector 160 in the distal direction until the threadsbetween the rod 152 and connector 160 run out. Further rotation causesthe plunger rod 152 and the first telescoping connector 160 to rotatetogether relative to the second telescoping connector 162, therebyaxially displacing the second telescoping connector 162 until thethreads between the first telescoping connector 160 and the secondtelescoping connector 162 run out. That is, the first connector 160 isthreadably coupled to the plunger rod 152 so that when the actuator 150rotates the plunger rod 152, the first connector 160 axially moves inthe distal direction until the first connector 160 reaches an end of itsaxial path. When the first connector 160 reaches the end of its axialpath, the first connector 160 begins to rotate together with the plungerrod 152, causing the second connector 162 to axially move in the distaldirection. While the illustrated assembly 142 includes two connectors160 and 162, another embodiment may include two or more connectors wherethe second connector 162 is connected to a third connector or a seriesof any number of additional telescoping connectors. The plunger 154,which is attached to a distal end 168 of the second telescopingconnector 162, drives through the reservoir 112 to expel the deliverablefluid 111. In FIG. 3, the plunger 154 is adjacent to the stopper 118 andin other embodiments, the plunger 154 may be integrally formed with orotherwise attached to the stopper 118 disposed in the reservoir 112. Tobypass the planetary gear coupler altogether, i.e. where the rotationalvelocity of the lead screw 122 does not need to increase or decrease,the lead screw 122 may be directly coupled to the telescoping plungerassembly 142. The drug delivery device 100 according to the presentdisclosure is not limited to the telescoping plunger assembly 142illustrated in FIGS. 2-5, and may include a different assembly thatactuates a plunger rod to drive a plunger or stopper through thereservoir 112.

While the illustrated drug delivery device 100 of FIGS. 2-5 includes atelescoping plunger assembly 142 and planetary gear coupler power pack141, the drive mechanism 120 may be coupled to a different epicyclicalpower pack and plunger assembly. For example, the rotating lead screw122 may be operably coupled to a power pack that can receive and convertan input rotational velocity to an output velocity to drive the plunger154 (or stopper 118 in FIG. 3) of the drug delivery device 100 throughthe reservoir 112. The rotational speed of the lead screw 122 may bevaried by increasing or decreasing the external threads 136 of the screw122. Additionally, the output rotational velocity may increase ordecrease according to changes in gear ratio and number of planetary gearcoupler stages. The planetary gear coupler 141 may be configured suchthat the output rotational velocity is greater than the input velocity,or the planetary gear coupler 141 may be configured such that the inputrotational velocity of the lead screw 122 is greater than the outputrotational velocity of the planetary gear coupler power pack 141.

Turning back to FIGS. 2 and 3, a clutch 166 may be mounted, or functionas a result of the lead screw material, to the lead screw 122 to reducethe rotational velocity of the lead screw 122 after the biasing device128 is released. The clutch 166 may be a mechanical clutch that providesa dampening or frictional force to the lead screw 122 as the lead screw122 rotates. For example, the clutch 166 may apply mechanical resistanceto the lead screw 122 by frictionally engaging the lead screw 122 andreducing the rotational velocity. The clutch 166 may apply the resistiveforce to the proximal end 132 or to the external threads 136 of the leadscrew 122. For example, in one embodiment, the clutch 166 can include aclutch pad that rests within a recess formed in the proximal end 132 ofthe lead screw 122 and which is operable through an adjustment mechanismmounted on the drug delivery device 100. The clutch pad can be springbiased against an internal sidewall of the drug delivery device 100 andthe lead screw 122, and the adjustment mechanism could include a setscrew that adjusts the tension of the spring and therefore the force theclutch pad applies to the lead screw 122. The set screw can in someversions be adjustable with a dial, a knob, or other manual device. Inother embodiments, the set screw can be adjustable with anelectromechanical switching device. Alternatively, the clutch 166 may bean electromechanical clutch that is electrically operated and appliesmechanical resistance to the rotating lead screw 122. For example, therotating shaft of the lead screw 122 may be aluminum and an appliedcurrent creates an electromagnetic flux, producing a regenerativebreaking mechanism via eddy currents. Alternatively, the applied currentcan produce an opposed rotational force to the lead screw 122.

In yet other embodiments, the clutch 166 may be an electromagneticclutch that generates a magnetic force to reduce the speed of the leadscrew 122. For example, the clutch 166 can include a magnet mounted inthe proximal end 132 of the lead screw 122 and a coil wrapped around theproximal end 132 of the lead screw 122. Applying a current to the coilcreates a magnetic field that can provide a resistance to rotation ofthe lead screw 122. Increasing the current can increase the resistance,for example. Such an electromagnetic clutch 166 may also be controlledby a dial or other user accessible device for adjusting the clutchingforce. By rotating the dial to a first position, the clutch may reducethe rotational velocity of the lead screw 122 by a first rate. The dialmay be rotated to one of a plurality of positions that correspond to aplurality of varying forces of resistance the clutch 166 may apply tothe lead screw 122. In this or in other embodiments, the drug deliverydevice may include a supercapacitor power source that stores theconverted kinetic energy of the biasing device 128 for reuse.

FIG. 6 illustrates a second exemplary drug delivery device 200 having arotatable drive mechanism 220 which powers drug delivery. For ease ofreference, and to the extent possible, the same or similar components ofthe drug delivery device of FIG. 6 will retain the same referencenumbers as outlined above with respect to the drug delivery device 100of FIG. 2 discussed above, although the reference numbers will beincreased by 100. Similar to the drug delivery devices 10 and 100 ofFIGS. 1-3, the drug delivery device 200 includes a drug reservoir 212having a glass barrel 213 that may be prefilled with a dispensable fluid211. The reservoir 212 is in fluid communication with a drug deliverymember 214 through which the dispensable fluid 211 is deliveredsubcutaneously to a patient. A plunger 218 disposed and movable withinthe reservoir 212 is configured to sealingly and slidably engage aninner wall of the glass barrel 213 to push the drug 211 through thereservoir 212 and out through an open end of the drug delivery member214. In the present disclosure, the plunger 218 is driven through thereservoir 212 by the rotatable drive mechanism 220.

The rotatable drive mechanism 220 shown in FIGS. 6-8, also referredherein as a drive assembly, includes a lead screw 222, a bearing 224, aball screw driver 226, a biasing device 228, and an activation device230. The lead screw 222 is a threaded shaft with a proximal end 232 anda distal end 234 and includes external threads 236 extending between theproximal and distal ends 232 and 234. In other embodiments, the leadscrew 222 may be partially threaded. As described in more detail below,the number of external threads 236 and spacing between the externalthreads 236 may vary depending on the drive force desired for injection.The ball screw driver 226 includes an aperture 238 having internalthreads 240 that engage the external threads 236 of the lead screw 222.The ball screw driver 226 and the lead screw 222 are coaxially alignedalong a longitudinal axis B of the drug delivery device 200 whenthreadably engaged.

As illustrated in FIGS. 6 and 7, the bearing 224 is spaced apart fromthe ball screw driver 226 by the biasing device 228. The biasing device228, which is a coil spring, generates an axial drive force F_(D) forbiasing the ball screw driver 226 away from the bearing 224 whenreleased by the activation device 230. The activation device 230 isconfigured to release the biasing device 228 from the compressedposition, as illustrated in FIGS. 6 and 7, to an extended position asshown in FIG. 8. As the biasing device 228 expands from the compressedposition, also referred herein as a preloaded position, to the extendedposition, the axial drive force F_(D) of the biasing device 228 causesthe ball screw driver 226 to axially move toward the distal end 234 ofthe lead screw 222, while simultaneously causing the lead screw 222 torotate such that a threaded engagement between the lead screw 222 andthe ball screw driver 226 bears the axial drive force F_(D). The bearing224 is operably attached, either by a ball bearing or other suitablemechanism, to the proximal end 232 of the lead screw 222, allowing thelead screw 222 to freely rotate without moving axially. The rotatabledrive mechanism 220 of the device in FIG. 6, and more specifically theexternal threads 236 of the lead screw 222, bears the axial drive forceF_(D) instead of the glass barrel 213 of the reservoir 212.

In FIG. 7, the activation device 230 is in the preloaded configurationand includes a button 233, an actuating spring 235, and a plurality oftabs 237. The actuating spring 235 is extended and disposed between thebutton 233 and the bearing 224. To release the biasing device 228, thebutton 233 is pressed downward, biasing the actuating spring 235 andoutwardly displacing the tabs 237 away from the ball screw driver 226and lead screw 222. The biasing device 228 is released by the tabs 237and expands into the extended position as shown in FIG. 8. Theactivation device 230 illustrated herein is merely an example and may beany device that can retain the compressed biasing device 228 and releasethe compressed spring 228 to the extended position for injection.

FIGS. 7 and 8 illustrate the drive mechanism 220 in the compressedposition (FIG. 7) and in the extended position (FIG. 8). The ball screwdriver 226 of the drug delivery device 200 of FIG. 6 may directly applya drive force to a plunger assembly 250 to drive the plunger 218 throughthe reservoir 212. The plunger assembly 250 includes a plunger rod 252,which may be a partially hollow cylinder, that surrounds the distal end232 of the lead screw 222. A proximal end 254 of the plunger rod 252 isadjacent to the ball screw driver 226 and a plunger end 256 is disposedat a distal end 258 of the plunger rod 252. In operation, the activationdevice 230 releases the biasing device 228, causing the lead screw 222to rotate and the ball screw driver 226 to axially move in the distaldirection. As the ball screw driver 226 moves toward the distal end 234of the lead screw 222, the ball screw driver 226 drives the plunger rod252 in the distal direction.

To vary the injection rate, the spring rate of the biasing device 228may be changed, and as mentioned earlier, the external threads 236 ofthe lead screw 222 may also vary. The rotational speed of the lead screw222 may vary by increasing the spacing between threads 236 and/ordecreasing or increasing the number of threads 236. For example, thedistance travelled by the ball screw driver 226 may be reduced bylimiting the extent of coverage of external threads 236 on the leadscrew 222. Limiting the threaded coverage of the lead screw 222 limitsthe distance the ball screw driver 226 can travel in the axialdirection, i.e. shortening the axial path of the ball screw driver 226.With fewer external threads 236, the ball screw driver 226 reaches theend of its axial path, i.e. the end of the external threads of the leadscrew 222, at a faster rate than if the axial path of the ball screwdriver 226 was the entire length of the lead screw 222. The shorter theaxial path of the ball screw driver 226, the faster the lead screw 222rotates, and the greater the force of the ball screw driver 226 impartsonto the plunger rod 252. In contrast, by increasing the number ofexternal threads 236, the ball screw driver 226 would take longer toreach the end of the axial path, thereby decreasing the rate at whichthe ball screw driver 226 impacts the plunger rod 252.

The plunger assembly 250 may be a single component, as illustrated inFIGS. 6-8, or may be an assembly of separate interconnected components.The plunger rod 252 may be removably attached to the ball screw driver226 at the proximal end 254 of the plunger rod 252. Alternatively, theproximal end 254 of the plunger rod 252 may be positioned adjacent butnot attached to the ball screw driver 226. In the embodiment illustratedin FIGS. 6-8, the plunger end 256 is separate and distinct from theplunger 218 disposed within the reservoir 212. In another embodiment,the plunger end 256 may be integrally formed with the plunger 218.

Turning back to FIG. 6, a clutch 266 may be mounted to the lead screw222 to reduce the rotational velocity of the lead screw 222 after thebiasing device 228 is released. The clutch 266 may be a mechanicalclutch that provides a dampening or frictional force to the lead screw222 as the lead screw 222 rotates. For example, the clutch 266 may applymechanical resistance to the rotation of the lead screw 222 byfrictionally engaging the lead screw 222 and reducing the rotationalvelocity. The clutch 266 may apply the resistive force to the proximalend 232 of the lead screw 222 or to the external threads 236.Alternatively, the clutch 266 may be a electromechanical clutch that iselectrically operated and applies a mechanical resistive force to therotating lead screw 222. In yet another embodiment, the clutch 266 maybe an electromagnetic clutch that directly applies a magnetic force toreduce the speed of the lead screw 222. Although not shown, the clutch266 may be manually controlled by a dial that is coupled to the clutch266. By rotating the dial to a first position, the clutch may reduce therotational velocity of the lead screw 222 by a first rate. The dial maybe rotated to one of a plurality of positions that correspond to aplurality of varying forces of resistance the clutch 266 may apply tothe lead screw 222.

The drug delivery devices 100 and 200 described herein allow forvariations in injection rate, deliverable volume, and drug viscosity.The injection rate may be varied by varying the gearing of the planetarygear coupler power pack 141 of the drug delivery device 100 of FIGS. 2-5and/or by varying the spring rate of the biasing devices 128 and 228, byvarying the configuration of the external threads 136 and 236 of thelead screws 122 and 222, or a combination thereof. The drug deliverydevices 100 and 200 do not require a motor nor do they impart a loadonto their respective syringes. Rather, the threaded engagement betweenthe lead screw 122 and 222 and the ball screw driver 126 and 226 bearthe force of the biasing device 128 and 228, and translate the force torotational or linear movement. The rotational motion of the lead screw122 and the linear movement of the ball screw driver 226 provide alow-impact, controlled, and safe drug delivery device.

FIG. 9 illustrates a drug delivery device 300 that may be poweredsimilarly as the drug delivery devices 100 and 200 of FIGS. 2 and 6, butincludes a different planetary gear coupler power pack 341, alsoillustrated in FIG. 10. For ease of reference, and to the extentpossible, the same or similar components of the drug delivery device ofFIG. 9 will retain the same reference numbers as outlined above withrespect to the drug delivery device 100 of FIG. 2 discussed above,although the reference numbers will be increased by 200.

In this embodiment, the planetary gear coupler 341 includes a planetaryring 374, a carrier arm 372, a plurality of connecting shafts 375,satellite gears 378, and a sun gear 376. The planetary ring 374 is fixedto a housing 370 of the device 300, and includes planetary gear teethV_(R) which engage with satellite gears teeth V_(P). The satellite gearteeth V_(P) also engage with gear teeth V_(S) of the sun gear 376. Whenthe planetary gear coupler 341 is activated, the carrier arm 372,satellite gears 378, and sun gear 376 rotate either clockwise orcounterclockwise about a longitudinal axis C of the drug delivery device300. The carrier arm 372 is threadably coupled to external threads 336of a lead screw 322, and rotates in a direction R_(C) as the lead screw322 rotates. As the carrier arm 372 rotates in the R_(C) direction, theconnectors shafts 375 connecting the carrier arm 372 and satellite gears378 cause the satellite gears 378 to rotate around the sun gear 376 inthe R_(P) direction. As the satellite gears 378 rotate in the R_(P)direction relative to the planetary ring 374, each of the satellitegears 378 spins about its axis D1, D2, and D3, thereby rotating the sungear 376 in a direction R_(S). The sun gear 376, which is coupled toexternal threads 353 of a plunger rod 352, rotates in the R_(S)direction to drive the plunger rod 352 axially in the distal direction.

An activation member 330 and a biasing member 328 operate to drive alead screw driver 326 to spin the lead screw 322 in the same or similarmanner as described previously with respect to the drug delivery devices100 and 200 of FIGS. 2-8. In this embodiment, the lead screw 322includes a hollow cavity sized to receive a portion of the plunger rod352. The plunger rod 352 is axially aligned with the lead screw 322along the longitudinal axis C, and includes external threads 353, aproximal end 354 disposed within the cavity of the lead screw 322, and adistal end 356 disposed within the reservoir 312. The sun gear 376 ofthe planetary gear coupler 341 is coupled to the external threads 353 ofthe plunger rod 352, and as the sun gear 376 rotates in the R_(S)direction, the plunger rod 352 moves in the distal direction and expelsthe drug 311 contained in the reservoir 312. The planetary gear coupler141 and 341 of the rotatable drive mechanism 120 and 320 may be used forincreasing and/or decreasing the impact of the initial drive force F_(D)of the biasing device 128 and 328 while providing a sufficient speed todrive the plunger rod through the drug delivery device 100 and 300. Inother words, the planetary gear coupler 141 and 341 may be usedprimarily as a drive transmission, which takes an input rotationalvelocity of the lead screw 122 and 322 and converts the rotationalmotion of the lead screw 122 and 322 to linear motion of the plunger rod152 and 352. Turning now to FIGS. 11 and 12, a different embodiment of arotatable drive mechanism 420 includes a planetary gear coupler 441directly coupled to an energy source to power drug delivery of a viscousdrug. For ease of reference, and to the extent possible, the same orsimilar components of the drug delivery device of FIGS. 11 and 12 willretain the same reference numbers as outlined above with respect to thedrug delivery device 300 of FIG. 9 discussed above, although thereference numbers will be increased by 100.

The drug delivery device 400 of FIG. 11 is powered by a constant forcespring 480, such as a watch spring, torsion spring, or a mechanicalpolar rotational propulsion source. In the illustrated embodiment, theconstant force spring is a torsion spring 480 which applies a constanttorque T to the planetary gear coupler 441 of the rotatable drivemechanism 420, which drives a lead screw 422 downward in the axialdirection. The torsion spring 480, which is fixed to a stationaryplanetary ring 474 and attached to a carrier arm 472, pushes against theplanetary ring 474 to rotate the carrier arm 472 in the R_(C2) directionabout a longitudinal axis E of the drug delivery device 400 when thetorsion spring 480 is released. As described previously with respect tothe planetary gear coupler 341 of FIGS. 9 and 10, the carrier arm 472drives a plurality of satellites gears 478 engaged with the planetaryring 474 and a sung gear 476. The carrier arm 472 rotates the satellitegears 478 in an R_(F2) direction, thereby causing the sun gear 476 torotate in an R_(S2) direction. Each of the satellite gears 478 rotateabout its axis G₁, G₂, and G₃ to rotate the sun gear 476 in the R_(S2)direction. As the sun gear 476 spins about the longitudinal axis E inthe R_(S2) direction, the lead screw 422, which may be attached to orintegral with a plunger rod, moves in the distal direction through thereservoir 412.

In the illustrated embodiment, the torsion spring 480 is indirectlycoupled to an activation member 430, which holds the lead screw 422stationary until the drug delivery device 400 is activated. Although theactivation member 430 in this embodiment is similar to the activationmember 30 of FIG. 1, the activation member 430 may be any mechanismknown in the art capable of releasing the torsion spring 480 on demand.Here, when a button 433 is pushed, the lead screw 422 is free to move,permitting the torsion spring 480 to expand from an initial compressedconfiguration to an expanded configuration. However, in anotherembodiment, the activation member 430 may be directly coupled to thetorsion spring 480 so that the torsion spring 480 is held in thecompressed configuration until the activation member 430 is activated.

To buffer the force of torque T provided by the torsion spring 480, theplanetary gear coupler 441 may incorporate a buffer element 486 as shownin a variation of the drug delivery device 400 in FIGS. 13 and 14. Theplanetary gear coupler 441 differs slightly from the planetary gearcoupler 441 of FIGS. 11 and 12, and is arranged differently in aninitial configuration and includes a split planetary ring 474. Thecarrier arm 472 and satellite gears 478 are slightly elevated relativeto the sun gear 476, and the split planetary ring 474 includes a firstportion 482 and a bottom portion 484 separated by a deformable bufferelement 486. The deformable buffer element 486 and the misalignedconfiguration of the planetary gear coupler 441 allow for the planetarygear coupler 441 to absorb any initial torsional shock of the torsionspring 480, and provide a clutching effect to the rotatable drivemechanism 420.

The bottom portion 484 of the planetary ring 474 is fixed to a housing470 of the drug delivery device 400, and the top portion 482 of the ring474 is rotatable relative to the housing 470. The top portion 482includes a tab 492 extending from the top portion 482 of the planetaryring 474 and disposed within a slotted groove 485 formed in the housing470 and shaped to guide the tab 492. So configured, as the torsion gear480 is released, the tab 492 of the top portion 482 of the planetaryring 474 the follows the slotted guide 485 of the housing 470, causingthe top portion 482 to rotate and travel downwardly to squeeze thebuffer element 486 between the top and bottom portions 482 and 484 ofthe planetary ring 474. As shown in the schematic of FIG. 14, the topportion 482 of the planetary ring 474 moves downward, compressing thebuffer element 486. Once the buffer element 486 reaches a particularpoint of compression, the top portion 482 no longer rotates and thesatellite gears 478 are aligned with the sun gear 476. The bufferelement 486 is disposed between a flexible washer 488, which alsodeforms as the top and bottom portions 482 and 484 squeeze the bufferelement 486 to absorb the torsional shock. The buffer element 486 may bean O-ring, bushing, washer, or other pliable material or seal, such asTeflon.

The planetary gear couplers 141, 341, and 441 described herein areconfigured to reduce overall weight of the mechanical power source ofthe drug delivery device 100, 300, 400, increase torque output, and/orincrease output velocity. The gear teeth ratios of the satellite gears146, 378, and 478, sun gears 144, 376, and 476, and planetary ring 374and 474 are determined to achieve any or all of these factors. In apreferred embodiment of the planetary gear couplers 341 and 441, theplanetary ring 374 and 474 are held stationary (or at least partiallystationary, as illustrated in FIGS. 13 and 14), and the gear teethratios of each gear may be the following: gear teeth V_(S) of the sungear 376 and 476 is 20; gear teeth V_(R) of the planetary ring 374 and474 is 48; gear teeth V_(R) of the satellite gears 378 and 478 is 16.This ratio may be found to increase torque output by 25% and decreasevelocity by 20% without increasing the overall weight of the drugdelivery device 300 and 400. While the planetary ring 374 and 474 isstationary in each of the planetary gear couplers 341 and 441, the sungear 376 and 476, may instead be held stationary. As such, the gearratios of each gear would be altered accordingly to achieve the desiredoutput velocity, torque, and/or overall weight.

The above description describes various systems for use with a drugdelivery device. It should be clear that the drug delivery device canfurther comprise use of a medicament listed below with the caveat thatthe following list should neither be considered to be all inclusive norlimiting. The medicament will be contained in a reservoir. In someinstances, the reservoir is a primary container that is either filled orpre-filled for treatment with the medicament. The primary container canbe a cartridge or a pre-filled syringe.

For example, the drug delivery device or more specifically the reservoirof the device may be filled with colony stimulating factors, such asgranulocyte colony-stimulating factor (G-CSF). Such G-CSF agentsinclude, but are not limited to, Neupogen® (filgrastim) and Neulasta®(pegfilgrastim). In various other embodiments, the drug delivery devicemay be used with various pharmaceutical products, such as anerythropoiesis stimulating agent (ESA), which may be in a liquid or alyophilized form. An ESA is any molecule that stimulates erythropoiesis,such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo®(epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta),Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon®(epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa),epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta),Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa,epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well asthe molecules or variants or analogs thereof as disclosed in thefollowing patents or patent applications: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689;and PCT Publication Nos. WO 91/05867; WO 95/05465; WO 96/40772; WO00/24893; WO 01/81405; and WO 2007/136752.

An ESA can be an erythropoiesis stimulating protein. As used herein,“erythropoiesis stimulating protein” means any protein that directly orindirectly causes activation of the erythropoietin receptor, forexample, by binding to and causing dimerization of the receptor.Erythropoiesis stimulating proteins include erythropoietin and variants,analogs, or derivatives thereof that bind to and activate erythropoietinreceptor; antibodies that bind to erythropoietin receptor and activatethe receptor; or peptides that bind to and activate erythropoietinreceptor. Erythropoiesis stimulating proteins include, but are notlimited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega,epoetin iota, epoetin zeta, and analogs thereof, pegylatederythropoietin, carbamylated erythropoietin, mimetic peptides (includingEMP1/hematide), and mimetic antibodies. Exemplary erythropoiesisstimulating proteins include erythropoietin, darbepoetin, erythropoietinagonist variants, and peptides or antibodies that bind and activateerythropoietin receptor (and include compounds reported in U.S.Publication Nos. 2003/0215444 and 2006/0040858,) as well aserythropoietin molecules or variants or analogs thereof as disclosed inthe following patents or patent applications: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086;6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369;7,030,226; 7,084,245; and 7,217,689; U.S. Publication Nos. 2002/0155998;2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694;2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834;2005/0096461; 2005/0107297; 2005/0107591; 2005/0124045; 2005/0124564;2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879; 2005/0158822;2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211;2005/0202538; 2005/0227289; 2005/0244409; 2006/0088906; and2006/0111279; and PCT Publication Nos. WO 91/05867; WO 95/05465; WO99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO2004/002417; WO 2004/002424; WO 2004/009627; WO 2004/024761; WO2004/033651; WO 2004/035603; WO 2004/043382; WO 2004/101600; WO2004/101606; WO 2004/101611; WO 2004/106373; WO 2004/018667; WO2005/001025; WO 2005/001136; WO 2005/021579; WO 2005/025606; WO2005/032460; WO 2005/051327; WO 2005/063808; WO 2005/063809; WO2005/070451; WO 2005/081687; WO 2005/084711; WO 2005/103076; WO2005/100403; WO 2005/092369; WO 2006/50959; WO 2006/02646; and WO2006/29094.

Examples of other pharmaceutical products for use with the device mayinclude, but are not limited to, antibodies such as Vectibix®(panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); otherbiological agents such as Enbrel® (etanercept, TNF-receptor/Fc fusionprotein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF,hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such asSensipar® (cinacalcet). The device may also be used with a therapeuticantibody, a polypeptide, a protein or other chemical, such as an iron,for example, ferumoxytol, iron dextrans, ferric glyconate, and ironsucrose. The pharmaceutical product may be in liquid form, orreconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins setforth below, including fusions, fragments, analogs, variants orderivatives thereof:

OPGL specific antibodies, peptibodies, and related proteins, and thelike (also referred to as RANKL specific antibodies, peptibodies and thelike), including fully humanized and human OPGL specific antibodies,particularly fully humanized monoclonal antibodies, including but notlimited to the antibodies described in PCT Publication No. WO 03/002713,such as OPGL specific antibodies and antibody related proteins,particularly those having the sequences set forth therein, particularly,but not limited to, those denoted therein: 9H7; 18B2; 2D8; 2E11; 16E1;and 22B3, including the OPGL specific antibodies having either the lightchain of SEQ ID NO:2 as set forth therein in FIG. 2 and/or the heavychain of SEQ ID NO:4, as set forth therein in FIG. 4;

Myostatin binding proteins, peptibodies, and related proteins, and thelike, including myostatin specific peptibodies, particularly thosedescribed in U.S. Publication No. 2004/0181033 and PCT Publication No.WO 2004/058988, particularly in parts pertinent to myostatin specificpeptibodies, including but not limited to peptibodies of the mTN8-19family, including those of SEQ ID NOS:305-351, including TN8-19-1through TN8-19-40, TN8-19 con1 and TN8-19 con2; peptibodies of the mL2family of SEQ ID NOS:357-383; the mL15 family of SEQ ID NOS:384-409; themL17 family of SEQ ID NOS:410-438; the mL20 family of SEQ IDNOS:439-446; the mL21 family of SEQ ID NOS:447-452; the mL24 family ofSEQ ID NOS:453-454; and those of SEQ ID NOS:615-631;

IL-4 receptor specific antibodies, peptibodies, and related proteins,and the like, particularly those that inhibit activities mediated bybinding of IL-4 and/or IL-13 to the receptor, including those describedin PCT Publication No. WO 2005/047331 or PCT Application No.PCT/US2004/37242 and in U.S. Publication No. 2005/112694, pertinent toIL-4 receptor specific antibodies, particularly such antibodies as aredescribed therein, particularly, and without limitation, thosedesignated therein: L1H1; L1H2; L1H3; L1H4; L1H5; L1H6; L1H7; L1H8;L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5; L2H6; L2H7; L2H8;L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1; L5H1; L6H1;

Interleukin 1-receptor 1 (“ID-R1”) specific antibodies, peptibodies, andrelated proteins, and the like, including but not limited to thosedescribed in U.S. Publication No. 2004/097712, n parts pertinent toIL1-R1 specific binding proteins, monoclonal antibodies in particular,especially, without limitation, those designated therein: 15CA, 26F5,27F2, 24E12, and 10H7;

Ang2 specific antibodies, peptibodies, and related proteins, and thelike, including but not limited to those described in PCT PublicationNo. WO 03/057134 and U.S. Publication No. 2003/0229023, pertinent toAng2 specific antibodies and peptibodies and the like, especially thoseof sequences described therein and including but not limited to: L1(N);L1(N) WT; L1(N) 1K WT; 2xL1(N); 2xL1(N) WT; Con4 (N), Con4 (N) 1K WT,2xCon4 (N) 1K; L1C; L1C 1K; 2xL1C; Con4C; Con4C 1K; 2xCon4C 1K; Con4-L1(N); Con4-L1C; TN-12-9 (N); C17 (N); TN8-8(N); TN8-14 (N); Con 1 (N),also including anti-Ang 2 antibodies and formulations such as thosedescribed in PCT Publication No. WO 2003/030833, particularly Ab526;Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545;Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ;AbFK; AbG1D4; AbGC1E8; AbH1C12; AbIA1; AbIF; AbIK, AbIP; and AbIP, intheir various permutations as described therein, n;

NGF specific antibodies, peptibodies, and related proteins, and the likeincluding, in particular, but not limited to those described in U.S.Publication No. 2005/0074821 and U.S. Pat. No. 6,919,426, particularlyas to NGF-specific antibodies and related proteins in this regard,including in particular, but not limited to, the NGF-specific antibodiestherein designated 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11;

CD22 specific antibodies, peptibodies, and related proteins, and thelike, such as those described in U.S. Pat. No. 5,789,554, as to CD22specific antibodies and related proteins, particularly human CD22specific antibodies, such as but not limited to humanized and fullyhuman antibodies, including but not limited to humanized and fully humanmonoclonal antibodies, particularly including but not limited to humanCD22 specific IgG antibodies, such as, for instance, a dimer of ahuman-mouse monoclonal hLL2 gamma-chain disulfide linked to ahuman-mouse monoclonal hLL2 kappa-chain, including, but limited to, forexample, the human CD22 specific fully humanized antibody inEpratuzumab, CAS registry number 501423-23-0;

IGF-1 receptor specific antibodies, peptibodies, and related proteins,and the like, such as those described in PCT Publication No. WO06/069202, including IGF-1 receptor specific antibodies and relatedproteins, including but not limited to the IGF-1 specific antibodiestherein designated L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9,L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18,L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27,L28H28, L29H29, L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36,L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45,L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, andIGF-1R-binding fragments and derivatives thereof;

Also among non-limiting examples of anti-IGF-1R antibodies for use inthe methods and compositions of the present invention are each and allof those described in:

(i) U.S. Publication No. 2006/0040358 (published Feb. 23, 2006),2005/0008642 (published Jan. 13, 2005), 2004/0228859 (published Nov. 18,2004), including but not limited to, for instance, antibody 1A (DSMZDeposit No. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM ACC 2589),antibody 23 (DSMZ Deposit No. DSM ACC 2588) and antibody 18 as describedtherein;

(ii) PCT Publication No. WO 06/138729 (published Dec. 28, 2006) and WO05/016970 (published Feb. 24, 2005), and Lu et al. (2004), J. Biol.Chem. 279:2856-2865, including but not limited to antibodies 2F8, A12,and IMC-A12 as described therein;

(iii) PCT Publication No. WO 07/012614 (published Feb. 1, 2007), WO07/000328 (published Jan. 4, 2007), WO 06/013472 (published Feb. 9,2006), WO 05/058967 (published Jun. 30, 2005), and WO 03/059951(published Jul. 24, 2003);

(iv) U.S. Publication No. 2005/0084906 (published Apr. 21, 2005),including but not limited to antibody 7C10, chimaeric antibody C7C10,antibody h7C10, antibody 7H2M, chimaeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version2, humanized antibody 7C10 version 3, and antibody 7H2HM, as describedtherein;

(v) U.S. Publication Nos. 2005/0249728 (published Nov. 10, 2005),2005/0186203 (published Aug. 25, 2005), 2004/0265307 (published Dec. 30,2004), and 2003/0235582 (published Dec. 25, 2003) and Maloney et al.(2003), Cancer Res. 63:5073-5083, including but not limited to antibodyEM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1,huEM164 v1.2, and huEM164 v1.3 as described therein;

(vi) U.S. Pat. No. 7,037,498 (issued May 2, 2006), U.S. Publication Nos.2005/0244408 (published Nov. 30, 2005) and 2004/0086503 (published May6, 2004), and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073,e.g., antibody CP-751,871, including but not limited to each of theantibodies produced by the hybridomas having the ATCC accession numbersPTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, andantibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3, asdescribed therein;

(vii) U.S. Publication Nos. 2005/0136063 (published Jun. 23, 2005) and2004/0018191 (published Jan. 29, 2004), including but not limited toantibody 19D12 and an antibody comprising a heavy chain encoded by apolynucleotide in plasmid 15H12/19D12 HCA (?4), deposited at the ATCCunder number PTA-5214, and a light chain encoded by a polynucleotide inplasmid 15H12/19D12 LCF (?), deposited at the ATCC under numberPTA-5220, as described therein; and

(viii) U.S. Publication No. 2004/0202655 (published Oct. 14, 2004),including but not limited to antibodies PINT-6A1, PINT-7A2, PINT-7A4,PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3,PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2,PINT-12A3, PINT-12A4, and PINT-12A5, as described therein; particularlyas to the aforementioned antibodies, peptibodies, and related proteinsand the like that target IGF-1 receptors;

B-7 related protein 1 specific antibodies, peptibodies, related proteinsand the like (“B7RP-1,” also is referred to in the literature as B7H2,ICOSL, B7h, and CD275), particularly B7RP-specific fully humanmonoclonal IgG2 antibodies, particularly fully human IgG2 monoclonalantibody that binds an epitope in the first immunoglobulin-like domainof B7RP-1, especially those that inhibit the interaction of B7RP-1 withits natural receptor, ICOS, on activated T cells in particular,especially, in all of the foregoing regards, those disclosed in U.S.Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, as tosuch antibodies and related proteins, including but not limited toantibodies designated therein as follow: 16H (having light chainvariable and heavy chain variable sequences SEQ ID NO:1 and SEQ ID NO:7respectively therein); 5D (having light chain variable and heavy chainvariable sequences SEQ ID NO:2 and SEQ ID NO:9 respectively therein); 2H(having light chain variable and heavy chain variable sequences SEQ IDNO:3 and SEQ ID NO:10 respectively therein); 43H (having light chainvariable and heavy chain variable sequences SEQ ID NO:6 and SEQ ID NO:14respectively therein); 41H (having light chain variable and heavy chainvariable sequences SEQ ID NO:5 and SEQ ID NO:13 respectively therein);and 15H (having light chain variable and heavy chain variable sequencesSEQ ID NO:4 and SEQ ID NO:12 respectively therein);

IL-15 specific antibodies, peptibodies, and related proteins, and thelike, such as, in particular, humanized monoclonal antibodies,particularly antibodies such as those disclosed in U.S. Publication Nos.2003/0138421; 2003/023586; and 2004/0071702; and U.S. Pat. No.7,153,507, as to IL-15 specific antibodies and related proteins,including peptibodies, including particularly, for instance, but notlimited to, HuMax IL-15 antibodies and related proteins, such as, forinstance, 146B7;

IFN gamma specific antibodies, peptibodies, and related proteins and thelike, especially human IFN gamma specific antibodies, particularly fullyhuman anti-IFN gamma antibodies, such as, for instance, those describedin U.S. Publication No. 2005/0004353, as to IFN gamma specificantibodies, particularly, for example, the antibodies therein designated1118; 1118*; 1119; 1121; and 1121*. The entire sequences of the heavyand light chains of each of these antibodies, as well as the sequencesof their heavy and light chain variable regions and complementaritydetermining regions, are each individually and as disclosed in theforegoing publication and in Thakur et al. (1999), Mol. Immunol.36:1107-1115. Specific antibodies include those having the heavy chainof SEQ ID NO:17 and the light chain of SEQ ID NO:18; those having theheavy chain variable region of SEQ ID NO:6 and the light chain variableregion of SEQ ID NO:8; those having the heavy chain of SEQ ID NO:19 andthe light chain of SEQ ID NO:20; those having the heavy chain variableregion of SEQ ID NO:10 and the light chain variable region of SEQ IDNO:12; those having the heavy chain of SEQ ID NO:32 and the light chainof SEQ ID NO:20; those having the heavy chain variable region of SEQ IDNO:30 and the light chain variable region of SEQ ID NO:12; those havingthe heavy chain sequence of SEQ ID NO:21 and the light chain sequence ofSEQ ID NO:22; those having the heavy chain variable region of SEQ IDNO:14 and the light chain variable region of SEQ ID NO:16; those havingthe heavy chain of SEQ ID NO:21 and the light chain of SEQ ID NO:33; andthose having the heavy chain variable region of SEQ ID NO:14 and thelight chain variable region of SEQ ID NO:31, as disclosed in theforegoing publication. A specific antibody contemplated is antibody 1119as disclosed in the foregoing U.S. publication and having a completeheavy chain of SEQ ID NO:17 as disclosed therein and having a completelight chain of SEQ ID NO:18 as disclosed therein;

TALL-1 specific antibodies, peptibodies, and the related proteins, andthe like, and other TALL specific binding proteins, such as thosedescribed in U.S. Publication Nos. 2003/0195156 and 2006/0135431, as toTALL-1 binding proteins, particularly the molecules of Tables 4 and 5B;

Parathyroid hormone (“PTH”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,756,480, particularly in parts pertinent to proteins that bind PTH;

Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,835,809, particularly in parts pertinent to proteins that bind TPO-R;

Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, andrelated proteins, and the like, including those that target theHGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonalantibodies that neutralize hepatocyte growth factor/scatter (HGF/SF)described in U.S. Publication No. 2005/0118643 and PCT Publication No.WO 2005/017107, huL2G7 described in U.S. Pat. No. 7,220,410 and OA-5d5described in U.S. Pat. Nos. 5,686,292 and 6,468,529 and in PCTPublication No. WO 96/38557, particularly in parts pertinent to proteinsthat bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins and thelike, such as those described in U.S. Pat. No. 7,521,048, particularlyin parts pertinent to proteins that bind TRAIL-R2;

Activin A specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. PublicationNo. 2009/0234106, particularly in parts pertinent to proteins that bindActivin A;

TGF-beta specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. Pat. No.6,803,453 and U.S. Publication No. 2007/0110747, particularly in partspertinent to proteins that bind TGF-beta;

Amyloid-beta protein specific antibodies, peptibodies, related proteins,and the like, including but not limited to those described in PCTPublication No. WO 2006/081171, particularly in parts pertinent toproteins that bind amyloid-beta proteins. One antibody contemplated isan antibody having a heavy chain variable region comprising SEQ ID NO:8and a light chain variable region having SEQ ID NO:6 as disclosed in theforegoing publication;

c-Kit specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2007/0253951, particularly in parts pertinent to proteins that bindc-Kit and/or other stem cell factor receptors;

OX40L specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2006/0002929, particularly in parts pertinent to proteins that bindOX40L and/or other ligands of the OX40 receptor; and

Other exemplary proteins, including Activase® (alteplase, tPA); Aranesp®(darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-1,Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonalantibody); Betaseron® (interferon-beta); Campath® (alemtuzumab,anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade®(bortezomib); MLN0002 (anti-?4ß7 mAb); MLN1202 (anti-CCR2 chemokinereceptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNFblocker); Eprex® (epoetin alfa); Erbitux® (cetuximab,anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human GrowthHormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb);Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab);insulin in solution; Infergen® (interferon alfacon-1); Natrecor®(nesiritide; recombinant human B-type natriuretic peptide (hBNP);Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide®(epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab,anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin);Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™(eculizumab); pexelizumab (anti-05 complement); Numax® (MEDI-524);Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio®(lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4);Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumabmertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega®(oprelvekin, human interleukin-11); Neulasta® (pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF,hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonalantibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNF?monoclonal antibody); Reopro® (abciximab, anti-GP Ilb/Ilia receptormonoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin®(bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect®(basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO(anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri®(natalizumab, anti-?4integrin mAb); Valortim® (MDX-1303, anti-B.anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab);Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portionof human IgG1 and the extracellular domains of both IL-1 receptorcomponents (the Type I receptor and receptor accessory protein)); VEGFtrap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab);Zenapax® (daclizumab, anti-IL-2R? mAb); Zevalin® (ibritumomab tiuxetan);Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonalantibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFcfusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNF?mAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb);HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab);M200 (volociximab, anti-?5?1 integrin mAb); MDX-010 (ipilimumab,anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficileToxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC);anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333(anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-CriptomAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019);anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb;anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb(MY0-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFN? mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1RmAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/IL23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10Ulcerative Colitis mAb (MDX-1100); anti-LLY antibody; BMS-66513;anti-Mannose Receptor/hCG? mAb (MDX-1307); anti-mesothelin dsFv-PE38conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFR?antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 humanmAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; anti-ZP3 mAb(HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2.

Also included can be a sclerostin antibody, such as but not limited toromosozumab, blosozumab, or BPS 804 (Novartis). Further included can betherapeutics such as rilotumumab, bixalomer, trebananib, ganitumab,conatumumab, motesanib diphosphate, brodalumab, vidupiprant,panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally,included in the device can be a monoclonal antibody (IgG) that bindshuman Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). Such PCSK9specific antibodies include, but are not limited to, Repatha®(evolocumab) and Praluent® (alirocumab), as well as molecules, variants,analogs or derivatives thereof as disclosed in the following patents orpatent applications: U.S. Pat. No. 8,030,547, U.S. Publication No.2013/0064825, WO2008/057457, WO2008/057458, WO2008/057459,WO2008/063382, WO2008/133647, WO2009/100297, WO2009/100318,WO2011/037791, WO2011/053759, WO2011/053783, WO2008/125623,WO2011/072263, WO2009/055783, WO2012/0544438, WO2010/029513,WO2011/111007, WO2010/077854, WO2012/088313, WO2012/101251,WO2012/101252, WO2012/101253, WO2012/109530, and WO2001/031007.

Also included can be talimogene laherparepvec or another oncolytic HSVfor the treatment of melanoma or other cancers. Examples of oncolyticHSV include, but are not limited to talimogene laherparepvec (U.S. Pat.Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (U.S. Pat. No. 7,981,669);OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143);G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002),Cancer Gene Ther., 9(12):967-978).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors ofmetalloproteinases (TIMPs) and are important in many natural processes.TIMP-3 is expressed by various cells or and is present in theextracellular matrix; it inhibits all the major cartilage-degradingmetalloproteases, and may play a role in role in many degradativediseases of connective tissue, including rheumatoid arthritis andosteoarthritis, as well as in cancer and cardiovascular conditions. Theamino acid sequence of TIMP-3, and the nucleic acid sequence of a DNAthat encodes TIMP-3, are disclosed in U.S. Pat. No. 6,562,596, issuedMay 13, 2003. Description of TIMP mutations can be found in U.S.Publication No. 2014/0274874 and PCT Publication No. WO 2014/152012.

Also included are antagonistic antibodies for human calcitoningene-related peptide (CGRP) receptor and bispecific antibody moleculethat target the CGRP receptor and other headache targets. Furtherinformation concerning these molecules can be found in PCT ApplicationNo. WO 2010/075238.

Additionally, bispecific T cell engager (BITE®) antibodies, e.g.BLINCYTO® (blinatumomab), can be used in the device. Alternatively,included can be an APJ large molecule agonist e.g., apelin or analoguesthereof in the device. Information relating to such molecules can befound in PCT Publication No. WO 2014/099984.

In certain embodiments, the medicament comprises a therapeuticallyeffective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLPreceptor antibody. Examples of anti-TSLP antibodies that may be used insuch embodiments include, but are not limited to, those described inU.S. Pat. Nos. 7,982,016, and 8,232,372, and U.S. Publication No.2009/0186022. Examples of anti-TSLP receptor antibodies include, but arenot limited to, those described in U.S. Pat. No. 8,101,182. Inparticularly preferred embodiments, the medicament comprises atherapeutically effective amount of the anti-TSLP antibody designated asA5 within U.S. Pat. No. 7,982,016.

At least some of the techniques of this disclosure similarly can beapplied to other drug delivery devices. For example, drug deliverydevices generally suitable for simulation using the techniques of thisdisclosure can include other hand-held injectors or on-body injectors.More generally, the techniques of this disclosure can be applied todevices in which a component that advances a liquid drug (or anotherliquid) uses coil compression, torsion, or another type of mechanicalenergy storage. Moreover, these techniques can be applied tonon-mechanical systems such as propellant-driven systems.

Although the autoinjectors and elements thereof, have been described interms of exemplary embodiments, they are not limited thereto. Thedetailed description is to be construed as exemplary only and does notdescribe every possible embodiment of the invention because describingevery possible embodiment would be impractical, if not impossible.Numerous alternative embodiments could be implemented, using eithercurrent technology or technology developed after the filing date of thispatent that would still fall within the scope of the claims defining theinvention.

It should be understood that the legal scope of the invention is definedby the words of the claims set forth at the end of this patentapplication. The appended claims should be construed broadly to includeother variants and embodiments of same, which may be made by thoseskilled in the art without departing from the scope and range ofequivalents of autoinjectors and their elements.

What is claimed:
 1. A drug delivery device comprising: a housing; a drugcontainer disposed within the housing and including a proximal end and adistal end; and a drive mechanism activatable to expel a drug from thedrug container, the drive mechanism comprising: a stopper movablydisposed within the drug container; a plunger configured to translate ina distal direction and rotate relative to the housing; a biasing memberoperably coupled to the plunger; and an annular member operably coupledto the plunger and rotationally fixed relative to the housing.
 2. Thedrug delivery device of claim 1, wherein the biasing member, via thedrive mechanism, is configured to rotate the plunger.
 3. The drugdelivery device of claim 1, wherein the annular member has a threadedinterior surface.
 4. The drug delivery device of claim 3, wherein thedrive mechanism comprises an elongate member having a threaded externalsurface threadingly engaged with the threaded interior surface of theannular member
 5. The drug delivery device of claim 4, wherein theelongate member directly coupled to the plunger to drive rotationthereof, such that the relative rotation of the elongate member and theplunger are the same.
 6. The drug delivery device of claim 3, wherein atleast a portion of the plunger has a threaded exterior surface.
 7. Thedrug delivery device of claim 6, wherein the plunger comprises atelescoping plunger assembly.
 8. The drug delivery device of claim 3,wherein the biasing device comprises a coil spring.
 9. The drug deliverydevice of claim 1, wherein the drive mechanism converts rotationalmotion into linear motion of the plunger.
 10. The drug delivery deviceof claim 1, wherein the drive mechanism comprises an elongate memberhaving a threaded external surface threadingly engaged with the threadedinterior surface of the annular member; and further comprising a couplerconfigured to receive a first rotational velocity from the elongatemember and deliver a second rotational velocity to the plunger.
 11. Thedrug delivery device of claim 1, further comprising an activation deviceoperably coupled to the drive mechanism to control activation thereof.12. The drug delivery device of claim 1, further comprising a drugdelivery member in fluid communication with the distal end of the drugcontainer.
 13. The drug delivery device of claim 1, further comprising adrug in the drug container.